Local anesthetics presently available are lacking in several ways. The duration of action is too short for acute (postoperative) and chronic pain therapy, the therapeutic to toxic ratio is such that maximum safe doses are sometimes therapeutically inadequate and local anesthetics do not discrminate between sensory, motor and autonomic fibers to any great degree. Thousands of compounds conforming to Lofgren's scheme for a true local anesthetic agent have been synthesized and tested over the past century with some notable results. But areas such as acute and chronic pain management and obstetrics still need better local anesthetics. This series of experiments is designed to synthesize and test a series of quaternary ammonium compounds (which have been demonstrated to have ultralong duration of action, three days to two weeks, good sensory/motor discrimination, and favorable therapeutic to toxic ratios in pilot studies) and study their potential for clinical application. This is a new direction in local anesthetic design which has been prompted by investigation dealing with the blockage of potassium in axons. At the same time we will continue to assess the feasibility of utilizing tetrodotoxin and saxitoxin in combination with conventional local anesthetics.